Programmed cell death in the nervous system—a programmed cell fate?

Abstract

Studies of developmental cell death in the nervous system have revealed two different modes of programmed cell death (PCD). One results from competition for target-derived trophic factors and leads to the stochastic removal of neurons and/or glia. A second, hard-wired form of PCD involves the lineage-specific, stereotypical death of identifiable neurons, glia or undifferentiated cells. Although traditionally associated with invertebrates, this "programmed PCD" can also occur in vertebrates. Recent studies have shed light on its genetic control, and have revealed that activation of the apoptotic machinery can be under the same complex, combinatorial control as the expression of terminal differentiation genes. This review will highlight these findings, and will suggest why such complex control evolved.

The labial gene is required to terminate proliferation of identified neuroblasts in postembryonic development of the Drosophila brain

“…For most of the neuroblasts of the central brain and thoracic ganglia, termination of proliferation is achieved by series of cellular adjustments, involving shrinkage, lengthening of the cell cycle, expression of nuclear prospero and then cell cycle exit via a symmetric final division (Maurange et al, 2008). In contrast, for neuroblasts in the abdominal ganglia, which cease dividing in larval stages, termination of proliferation involves another mechanism, namely induction of programmed cell death in neuroblasts through expression of Hox gene-encoded transcription factors (reviewed by Pearson et al, 2005; Rogulja-Ortmann and Technau, 2008; Miguel-Aliaga and Thor, 2009; Sousa-Nunes et al, 2010). More specifically, in all neuroblasts of the central abdomen, the Hox gene abdominal-A ( abd-A ) is expressed in a short pulse during larval development in order to trigger programmed cell death (Bello et al, 2003).…”

Iodine deficiency increases apoptosis and decreases synaptotagmin-1 and PSD-95 in rat hippocampus

“…33,34 So we detected apoptosis to study the status of neural development of rat hippocampus. ID and PTU treatment increased cell apoptosis in hippocampal CA1, CA3, and DG regions.…”

Subtype-specific neuronal remodeling duringDrosophilametamorphosis

“…These examples indicate a role for subtype transcription factors in subtype PCD (reviewed in ref. 42), but we have yet to determine how such factors studies of ecdysone-induced PCD of other Drosophila tissues offer potential clues for how PCD may be activated. 13 Direct binding of EcR-B1 to EcR-response elements (EcR-RE) in the cis-regulatory regions of reaper and dronc is required for their expression and subsequent PCD of salivary glands.…”

“…42). The sensory-neuron determinant transcription factor senseless has been implicated in the protection of a subset of Bolwig's organ photoreceptor neurons from PCD at pupariation.…”

“…In such cases, newly born postmitotic neurons utilize transcription factors mostly associated with subtype fate determination to regulate hard-wired PCD. 42 These include transcription factors that direct lineage-and/or segmentspecific cell fates. 43,44 As the metamorphic PCD of specific vCrz and RP2 neurons is highly subtype-or segment-specific 11,12 we would predict that integration of subtypetranscription factor codes with ecdysonetriggered cascades of nuclear receptors determines which neuronal subtypes undergo metamorphic PCD.…”